The article by Blaszyk and Björnsson1 in the December issue of the ARCHIVES is one of many recently published concerning the factor V Leiden (FVL) mutation. The "big three" of thrombophilias (hypercoagulability states) used to be antithrombin deficiency, deficiency of protein C, and deficiency of protein S. Antithrombin III inactivates clotting factors Xa and XIII; although most patients have an acquired deficit, approximately 1 in 1000 individuals in the United States have a congenital deficit with an identified genetic defect (an autosomal dominant). Likewise, protein C and S deficits are ordinarily acquired (commonly from vitamin K deficiency) but can be inherited; these factors interfere with blood clotting by blocking factors V and VIII in the intrinsic cascade. The fourth and most common inheritable thrombophilia is now the FVL mutation, which results in resistance to activated protein C with the potential for causing spontaneous intravascular clotting. This is manifested primarily as spontaneous venous thrombosis but can occasionally cause pulmonary embolus and, less commonly, arterial obstruction.
Baker RJ. Treatment Considerations for Inherited Thrombophilia and Pulmonary Embolus. Arch Surg. 2001;136(2):237. doi:10.1001/archsurg.136.2.237